Annals of Diagnostic Pathology最新文献_第5页

Diagnostic immunohistochemistry use in Belgian laboratories 比利时实验室使用的诊断性免疫组化技术。

IF 1.5 4区医学 Q3 PATHOLOGY

Annals of Diagnostic Pathology

Pub Date : 2024-10-30 DOI: 10.1016/j.anndiagpath.2024.152388

Christophe de Meester, Elena Costa, Claudia Schönborn, Lorena San Miguel

Objectives

In Belgium, the use of IHC testing has grown in the last decade. However, there is a lack of information on the specific indications for which it is reimbursed. The aim of the study is to offer an overview on the use of diagnostic inmunohistochemistry (IHC) testing and its recent trends.

Methods

Our analysis is limited to reimbursed use, which in Belgium is restricted to a maximum of 4 different IHC stains per sampling session for diagnostic IHC. Consulted sources included data from the compulsory health insurance, and data extracted from a sample of pathology reports gathered from Belgian laboratories for the year 2019.

Results

Over the last 10 years, the use of IHC in Belgium grew from 729 030 stains in 2012 to 1,194,331 in 2019, an increase of 63.8 % while the increase in the number of histological or cytological examinations was 13.3 %. The main stains used in 2019 were H. pylori, Ki-67 and broad spectrum CK, which were used in multiple body sites, reflecting the difficulties to identify specific indications. The gastro-intestinal tract is the body site with the highest number of IHC stains (38.2 % of all stains performed), and the most frequently used stain in gastro intestinal biopsies were H. pylori (43.1 %), and CD3 (6.8 %).

Conclusion

This study offers an overview of the most frequent indications for which diagnostic IHC staining is used in Belgium, and reflects the evolving nature of this field, highlighting the importance to increase clarity and improve data collection.

目的：在比利时，IHC 检测的使用在过去十年中有所增长。然而，关于其报销的具体适应症却缺乏相关信息。本研究旨在概述诊断性免疫组化（IHC）检测的使用情况及其最新趋势：我们的分析仅限于有偿使用，在比利时，诊断性 IHC 每次取样最多只能使用 4 种不同的 IHC 染色剂。参考来源包括强制医疗保险的数据，以及从比利时实验室收集的2019年病理报告样本中提取的数据：在过去10年中，比利时的IHC使用量从2012年的729 030种染色剂增加到2019年的1 194 331种，增幅为63.8%，而组织学或细胞学检查的数量增幅为13.3%。2019年使用的主要染色剂是幽门螺杆菌、Ki-67和广谱CK，它们被用于多个身体部位，反映出难以确定特定适应症。胃肠道是IHC染色最多的身体部位（占所有染色的38.2%），胃肠道活检中最常用的染色为幽门螺杆菌（43.1%）和CD3（6.8%）：本研究概述了比利时最常用的诊断性 IHC 染色适应症，反映了该领域不断发展的性质，强调了提高清晰度和改进数据收集的重要性。

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引用次数: 0

Histomorphology based prediction of p16 immunopositivity and p16/HPV DNA co-positivity in oral squamous cell carcinoma 基于组织形态学预测口腔鳞状细胞癌的 p16 免疫阳性率和 p16/HPV DNA 共阳性率

IF 1.5 4区医学 Q3 PATHOLOGY

Annals of Diagnostic Pathology

Pub Date : 2024-10-24 DOI: 10.1016/j.anndiagpath.2024.152389

Farhat Naz , Nadeem Tanveer , Hitesh Verma , Sudheer Arava , Aanchal Kakkar , Shivam Pandey , Harsh Goel , Amar Ranjan , Anita Chopra , Pranay Tanwar

The histomorphological features predictive of p16 and human papilloma virus (HPV DNA) positivity in oropharyngeal carcinoma have been a matter of much debate. However, only few studies have been done on oral squamous cell carcinoma (OSCC) to correlate the histomorphological features with p16 and HPV DNA positivity. Oral squamous cell carcinoma has distinct etiopathogenesis, treatment and prognosis as compared to oropharyngeal carcinomas.

A total of 800 oral squamous cell carcinoma biopsy cases were evaluated for features suggestive of HPV infection like basaloid appearance, absence of stromal reaction, nests and lobules of tumor cells with pushing borders, central necrosis, lympho-epithelial morphology, koilocytes, and non-keratinizing or hybrid morphology. Immunohistochemistry was performed for p16 expression (E6H4 clone, CINtec histology, Roche diagnostics). The cases which showed 2+/3+ (from moderate to high intensity) staining with >75 % cells were considered as p16 immunopositive. All the p16 immunopositive cases were subjected to real-time PCR (polymerase chain reaction) for HPV DNA detection to confirm HPV positivity. A total of 139 (17.37 %) OSCC cases were p16 immunopositive and out of these 104 (104/139, 74.8 %) cases showed HPV-DNA PCR positivity. None of the features were found to be predictive on multivariate logistic regression analysis. However, on bivariable analysis, nest/lobule with pushing border was the only histopathological feature which had a significant correlation with p16 immunopositivity (P value = 0.0001) and p16 and HPV DNA copositivity (P value = 0.0001). (Fisher's exact test -two tailed).

To conclude-morphology is not really predictive of HPV positivity in OSCC cases. Only one feature- nests and lobule with pushing border is suggestive on bivariable analysis.

口咽癌中可预测 p16 和人乳头状瘤病毒（HPV DNA）阳性的组织形态学特征一直是一个争论不休的问题。然而，只有少数研究对口腔鳞状细胞癌（OSCC）的组织形态特征与 p16 和 HPV DNA 阳性进行了相关性分析。共对 800 例口腔鳞状细胞癌活检病例进行了评估，以确定是否存在提示 HPV 感染的特征，如基底样外观、无基质反应、肿瘤细胞巢状和小叶状且边界推动、中央坏死、淋巴上皮形态、绒毛细胞、非角化或混合形态。免疫组化检测 p16 表达（E6H4 克隆，CINtec 组织学，罗氏诊断公司）。显示 2+/3+（从中度到高度）染色且细胞占 75% 的病例被视为 p16 免疫阳性。对所有 p16 免疫阳性病例进行实时 PCR（聚合酶链反应）HPV DNA 检测，以确认 HPV 阳性。共有 139 例（17.37%）OSCC 病例 p16 免疫阳性，其中 104 例（104/139，74.8%）显示 HPV-DNA PCR 阳性。在多变量逻辑回归分析中，没有发现任何特征具有预测性。然而，在双变量分析中，巢状/小叶状推移边界是唯一与 p16 免疫阳性（P 值 = 0.0001）和 p16 与 HPV DNA 共阳性（P 值 = 0.0001）有显著相关性的组织病理学特征。(总之，形态学并不能真正预测 OSCC 病例中的 HPV 阳性。在双变量分析中，只有一个特征--巢状和边界推移的小叶--具有提示性。

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引用次数: 0

Prognostic significance of CD3+ and CD8+ T-cells immunoscore in renal cell carcinoma: A comparison between two simple models for assessment 肾细胞癌中 CD3+ 和 CD8+ T 细胞免疫评分的预后意义：两种简单评估模型的比较。

IF 1.5 4区医学 Q3 PATHOLOGY

Annals of Diagnostic Pathology

Pub Date : 2024-10-22 DOI: 10.1016/j.anndiagpath.2024.152387

Amira Emad Elwy , Mahmoud Ismail Nassar , Shimaa Hassan Shaban , Tarek Mohamed Elsaba

The immunoscore (ISc) has been extensively investigated as a prognostic indicator for numerous solid tumors. In renal cell carcinoma (RCC), its prognostic significance has been evaluated in a small number of studies. This study was designed to ascertain the prognostic value of ISc based on CD3+ and CD8+ T cells in patients with RCC. This study included 115 non-metastatic RCC patients who underwent nephrectomy. The ISc was obtained by estimating the densities of CD3+ and CD8+ cells at the invasive margin and center of the tumor using two methods: cell count per square millimeter (cell count/mm²) and percentage of cells per square millimeter (% of cells/mm²). The patients were categorized into low and high groups according to the ISc. The associations between the ISc and clinicopathological characters, including survival, were analyzed statistically. Adverse clinicopathologic factors were significantly associated with high ISc. Patients with high ISc had significantly worse overall survival (OS) and disease-free survival (DFS) rates over three years (p < 0.001). High ISc was considered a predictor of shortened DFS in univariate analysis (p < 0.001). However, in multivariate analysis, it was a dependent predictor. High ISc could help identify individuals more likely to develop recurrence and may impact treatment strategy for more effective personalized care. Moreover, establishing a modified objective, automated, digital quantification method of immune cells (% of cells/mm² instead of cell count/mm²) is expected to be simple to implement in routine, highly affordable, time efficient, clinically meaningful, and will improve assay performance.

免疫评分（ISc）作为许多实体瘤的预后指标已被广泛研究。在肾细胞癌（RCC）中，只有少数研究对其预后意义进行了评估。本研究旨在确定基于 CD3+ 和 CD8+ T 细胞的 ISc 对 RCC 患者的预后价值。这项研究纳入了115名接受肾切除术的非转移性RCC患者。ISC是通过估算肿瘤浸润边缘和中心的CD3+和CD8+细胞密度得出的，采用了两种方法：每平方毫米细胞计数（细胞计数/mm2）和每平方毫米细胞百分比（细胞百分比/mm2）。根据 ISc 将患者分为低度组和高度组。统计分析了 ISc 与临床病理特征（包括存活率）之间的关系。不良临床病理因素与高ISc显著相关。高 ISc 患者三年内的总生存率（OS）和无病生存率（DFS）明显较差（p 2）。

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引用次数: 0

Metastatic tumours to the parotid: A 20-year single institutional experience with an emphasis on 14 unusual presentations 腮腺转移性肿瘤：20年的单一机构经验，重点关注14种不寻常表现。

IF 1.5 4区医学 Q3 PATHOLOGY

Annals of Diagnostic Pathology

Pub Date : 2024-10-19 DOI: 10.1016/j.anndiagpath.2024.152386

Prilla P.M. Tsang, Garima Gupta, Suchana Mukhopadhyay

The parotid gland is a rare site for distant metastasis. We aim to provide an overview of metastatic tumours to the parotid over the past 20 years, focusing on clinicopathological analysis of 14 rare diagnoses. To the best of our knowledge, we are the first group to present the most up-to-date and largest case series on unusual metastases to the parotid. A total of 93 metastatic cases were identified from 2004 to 2023, on the pathology information system at North West London Pathology, with squamous cell carcinoma (n = 45, 48.4 %) as the most common primary, followed by malignant melanoma (n = 29, 31.2 %) and Merkel cell carcinoma (n = 4, 4.3 %). We came across 14 rare tumours that had metastasised to the parotid, including metastatic adenocarcinoma from kidney (n = 3, 3.2 %), lung (n = 3, 3.2 %) and breast (n = 1, 1.1 %), olfactory neuroblastoma (n = 3, 3.2 %), soft tissue sarcoma (n = 2, 2.2 %), small cell carcinoma (n = 1, 1,1 %) and hidradenocarcinoma (n = 1, 1.1 %). Half of all secondary neoplastic lesions (50.5 %) were found in intra-parotid nodes, while the other half (49.5 %) were found in parotid parenchyma. Our study offers valuable insights into the various tumour types that can metastasise to the parotid across a wide age range. It underscores the necessity of maintaining a broad differential diagnosis. Keeping an open mind regarding the potential primary sources of the tumour is imperative for accurate diagnosis and effective treatment planning.

腮腺是一个罕见的远处转移部位。我们旨在概述过去 20 年中腮腺转移性肿瘤的情况，重点对 14 例罕见诊断进行临床病理分析。据我们所知，我们是第一个对腮腺异常转移进行最新、最大规模病例系列研究的小组。从2004年到2023年，我们在伦敦西北病理科的病理信息系统上共发现了93例转移病例，其中鳞状细胞癌（45例，占48.4%）是最常见的原发肿瘤，其次是恶性黑色素瘤（29例，占31.2%）和梅克尔细胞癌（4例，占4.3%）。我们发现了 14 例转移到腮腺的罕见肿瘤，包括来自肾脏（3 例，占 3.2%）、肺部（3 例，占 3.2%）和乳腺（1 例，占 1.1 %）、嗅神经母细胞瘤（n = 3，3.2 %）、软组织肉瘤（n = 2，2.2 %）、小细胞癌（n = 1，1.1 %）和隐腺癌（n = 1，1.1 %）。所有继发性肿瘤病变中有一半（50.5%）发生在腮腺内结节，另一半（49.5%）发生在腮腺实质。我们的研究为了解不同年龄段腮腺转移的各种肿瘤类型提供了有价值的见解。它强调了保持广泛鉴别诊断的必要性。对肿瘤的潜在原发来源保持开放的心态是准确诊断和有效治疗计划的必要条件。

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引用次数: 0

Gelatinous transformation of bone marrow associated with ring sideroblasts: A diagnostic pitfall 与环形红细胞相关的骨髓凝胶样变：诊断陷阱

IF 1.5 4区医学 Q3 PATHOLOGY

Annals of Diagnostic Pathology

Pub Date : 2024-10-17 DOI: 10.1016/j.anndiagpath.2024.152385

Mahreen Hussain , Faisal Rawas , Joseph Gosnell , Leonard J. Medeiros , Kirill A. Lyapichev

Gelatinous bone marrow transformation (GBMT) is a rare condition characterized by adipocyte atrophy, deposition of extracellular gelatinous substance in the bone marrow and associated hypoplastic hematopoiesis. The underlying pathogenic mechanisms of GBMT remain poorly understood. Here we describe 3 cases of GBMT associated with ring sideroblasts. An electronic search of institutional archives was conducted via the laboratory information system to identify patients with a body mass index (BMI) of <18.5 who underwent bone marrow evaluation. The slides and reports for these bone marrow specimens were reviewed. Bone marrow specimens of 10 patients were identified and reviewed. Three (30 %) were found to have GBMT and ring sideroblasts, ranging from 2 to 20 %. Blasts were not increased and there was no other morphologic evidence of dysplasia. Every patient had one or more peripheral blood cytopenias. In one patient, copper deficiency was proven providing an explanation for the ring sideroblasts. To the best of our knowledge, ring sideroblasts have not been well documented in GBMT and aims to contribute to a better understanding of disease recognition and pathogenesis and also to prevent potential misdiagnosis as a myelodysplastic syndrome.

凝胶状骨髓转化（GBMT）是一种罕见的疾病，其特征是脂肪细胞萎缩、骨髓中细胞外凝胶状物质沉积以及相关的造血功能低下。人们对 GBMT 的潜在致病机制仍知之甚少。在此，我们描述了 3 例与环状巩膜母细胞相关的 GBMT 病例。我们通过实验室信息系统对机构档案进行了电子搜索，以确定体重指数（BMI）为

{"title":"Gelatinous transformation of bone marrow associated with ring sideroblasts: A diagnostic pitfall","authors":"Mahreen Hussain , Faisal Rawas , Joseph Gosnell , Leonard J. Medeiros , Kirill A. Lyapichev","doi":"10.1016/j.anndiagpath.2024.152385","DOIUrl":"10.1016/j.anndiagpath.2024.152385","url":null,"abstract":"<div><div>Gelatinous bone marrow transformation (GBMT) is a rare condition characterized by adipocyte atrophy, deposition of extracellular gelatinous substance in the bone marrow and associated hypoplastic hematopoiesis. The underlying pathogenic mechanisms of GBMT remain poorly understood. Here we describe 3 cases of GBMT associated with ring sideroblasts. An electronic search of institutional archives was conducted via the laboratory information system to identify patients with a body mass index (BMI) of <18.5 who underwent bone marrow evaluation. The slides and reports for these bone marrow specimens were reviewed. Bone marrow specimens of 10 patients were identified and reviewed. Three (30 %) were found to have GBMT and ring sideroblasts, ranging from 2 to 20 %. Blasts were not increased and there was no other morphologic evidence of dysplasia. Every patient had one or more peripheral blood cytopenias. In one patient, copper deficiency was proven providing an explanation for the ring sideroblasts. To the best of our knowledge, ring sideroblasts have not been well documented in GBMT and aims to contribute to a better understanding of disease recognition and pathogenesis and also to prevent potential misdiagnosis as a myelodysplastic syndrome.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"73 ","pages":"Article 152385"},"PeriodicalIF":1.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The usefulness of evaluating PTEN expression for accurate grading of phyllodes tumors 评估 PTEN 表达对植物瘤准确分级的作用。

IF 1.5 4区医学 Q3 PATHOLOGY

Annals of Diagnostic Pathology

Pub Date : 2024-10-16 DOI: 10.1016/j.anndiagpath.2024.152384

Donghyun Kim , Kwang-Sun Suh , Mee-Ran Kim , Song-Yi Choi

Phyllodes tumors (PTs) are classified as benign, borderline, or malignant based on histologic characteristics. However, because histological criteria are subjective and diagnosis requires integrating multiple findings, discrepancies often occur between observers. Therefore, it is necessary to discover biomarkers based on the molecular characteristics of PTs. This study aimed to identify dysregulated microRNAs (miRNAs) in PTs through miRNA profiling and determine whether expression of their target genes could be useful as PT biomarkers. MiRNA profiling was performed on 13 PTs (three malignant, three borderline, seven benign) and six fibroadenomas, and predicted target genes of dysregulated miRNAs were selected using three computation algorithms. The expression of two miRNAs, miR-155 and miR-200c, was 1.69-fold and 1.61-fold higher, respectively, in borderline and malignant PT groups than in the benign PT group (p < 0.05). KEGG pathway analysis revealed that the 374 target genes of these two miRNAs (miR-155 and miR200c) participated in several signaling pathways, adherens junction, cell cycle, and pathway in cancer. Immunohistochemical staining for PTEN, one of candidate target genes of miR-200c, was performed on whole slides of PT tissue classified as malignant (n = 9), borderline (n = 12), or benign (n = 21). Stromal tumor cells of high-grade PTs (borderline and malignant) had significantly lower PTEN expression than those of low-grade PTs (benign) (p-value ≤0.001). Semiquantitative analysis of PTEN expression, score 0–8, revealed that it correlated with histologic findings. Low PTEN expression (s-score of 6 or less) was used as a diagnostic criterion for high-grade PTs, it showed 100 % sensitivity and 95.2 % specificity in 42 cases of PTs. Currently, PT grading based solely on subjective histologic findings is challenging, but semiquantitative PTEN expression analysis could provide a more accurate and objective way to grade PTs.

皮样瘤（PT）根据组织学特征分为良性、边缘性和恶性。然而，由于组织学标准是主观的，而且诊断需要综合多种发现，因此观察者之间经常会出现分歧。因此，有必要根据 PT 的分子特征发现生物标志物。本研究旨在通过miRNA图谱分析鉴定PT中失调的microRNA（miRNA），并确定其靶基因的表达是否可作为PT的生物标志物。研究人员对13例PT（3例恶性、3例边缘性、7例良性）和6例纤维腺瘤进行了miRNA图谱分析，并利用三种计算算法筛选出调控失调miRNA的预测靶基因。miR-155和miR-200c这两种miRNA在边缘型和恶性PT组的表达量分别是良性PT组的1.69倍和1.61倍（P＜0.05）。

{"title":"The usefulness of evaluating PTEN expression for accurate grading of phyllodes tumors","authors":"Donghyun Kim , Kwang-Sun Suh , Mee-Ran Kim , Song-Yi Choi","doi":"10.1016/j.anndiagpath.2024.152384","DOIUrl":"10.1016/j.anndiagpath.2024.152384","url":null,"abstract":"<div><div>Phyllodes tumors (PTs) are classified as benign, borderline, or malignant based on histologic characteristics. However, because histological criteria are subjective and diagnosis requires integrating multiple findings, discrepancies often occur between observers. Therefore, it is necessary to discover biomarkers based on the molecular characteristics of PTs. This study aimed to identify dysregulated microRNAs (miRNAs) in PTs through miRNA profiling and determine whether expression of their target genes could be useful as PT biomarkers. MiRNA profiling was performed on 13 PTs (three malignant, three borderline, seven benign) and six fibroadenomas, and predicted target genes of dysregulated miRNAs were selected using three computation algorithms. The expression of two miRNAs, miR-155 and miR-200c, was 1.69-fold and 1.61-fold higher, respectively, in borderline and malignant PT groups than in the benign PT group (<em>p</em> < 0.05). KEGG pathway analysis revealed that the 374 target genes of these two miRNAs (miR-155 and miR200c) participated in several signaling pathways, adherens junction, cell cycle, and pathway in cancer. Immunohistochemical staining for PTEN, one of candidate target genes of miR-200c, was performed on whole slides of PT tissue classified as malignant (<em>n</em> = 9), borderline (<em>n</em> = 12), or benign (<em>n</em> = 21). Stromal tumor cells of high-grade PTs (borderline and malignant) had significantly lower PTEN expression than those of low-grade PTs (benign) (<em>p</em>-value ≤0.001). Semiquantitative analysis of PTEN expression, score 0–8, revealed that it correlated with histologic findings. Low PTEN expression (s-score of 6 or less) was used as a diagnostic criterion for high-grade PTs, it showed 100 % sensitivity and 95.2 % specificity in 42 cases of PTs. Currently, PT grading based solely on subjective histologic findings is challenging, but semiquantitative PTEN expression analysis could provide a more accurate and objective way to grade PTs.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"73 ","pages":"Article 152384"},"PeriodicalIF":1.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinicopathological analysis of primary central nervous system lymphoma in patients with or without HIV infection 感染或未感染艾滋病毒患者原发性中枢神经系统淋巴瘤的临床病理分析

IF 1.5 4区医学 Q3 PATHOLOGY

Annals of Diagnostic Pathology

Pub Date : 2024-10-11 DOI: 10.1016/j.anndiagpath.2024.152383

Man Li , Jiamin Chen , Peng Wang , Enshan Feng , Xiangmei Chen , Haili Gao , Zhiyuan Ma , Xingang Zhou

The clinicopathological features of HIV-related primary central nervous system lymphoma (PCNSL) and immunocompetent primary central nervous system lymphoma (IC-PCNSL) were found to be distinct. Thirty-seven patients with HIV-related PCNSL and thirty patients with IC-PCNSL were included in our study. Hematoxylin & eosin (HE) staining, immunohistochemical detection using CD10, MUM1, CD20, Bcl-2, Bcl-6, p53, C-MYC, Ki67, methyltransferase like factor 3 (METTL3) antibodies and Epstein–Barr encoding region (EBER) in situ hybridization were performed. All of the patients were classified as the diffuse large B-cell lymphoma (DLBCL) histological type. Patients with HIV-related PCNSL were younger and more likely to be male, with elevated lactate dehydrogenase (LDH) and low sugar content in cerebrospinal fluid (CSF) compared to patients with IC-PCNSL.The positive rates of METTL3, Bcl-2, p53 and EBER were significantly higher in HIV-related PCNSL patients than in IC-PCNSL patients. Furthermore, we also found that the expression of METTL3 was lower in germinal centre B-cell (GCB)-like DLBCL (n = 7) than in non-GCB like DLBCL (n = 30) in HIV-related PCNSL (P = 0.030); however, in IC-PCNSL patients, the expression of METTL3 was not significantly different between GCB-like DLBCL and non-GCB-like DLBCL (P = 0.670). Although the manifestations are similar in PCNSL patients with and without HIV, HIV-related PCNSL differs from IC-PCNSL in terms of pathological characteristics including METTL3, Bcl-2, p53 and EBER. We therefore suggest that the pathogenesis of HIV-related PCNSL and IC-PCNSL may differ according to host immune status.

研究发现，HIV相关原发性中枢神经系统淋巴瘤（PCNSL）和免疫功能正常原发性中枢神经系统淋巴瘤（IC-PCNSL）的临床病理特征截然不同。我们的研究纳入了 37 例 HIV 相关 PCNSL 患者和 30 例 IC-PCNSL 患者。研究人员对患者进行了血沉和伊红（HE）染色，使用 CD10、MUM1、CD20、Bcl-2、Bcl-6、p53、C-MYC、Ki67、甲基转移酶样因子 3（METTL3）抗体进行了免疫组化检测，并进行了 Epstein-Barr 编码区（EBER）原位杂交。所有患者均被归类为弥漫大B细胞淋巴瘤（DLBCL）组织学类型。与IC-PCNSL患者相比，HIV相关PCNSL患者更年轻，更可能是男性，乳酸脱氢酶（LDH）升高，脑脊液（CSF）中糖含量低。此外，我们还发现，在HIV相关PCNSL患者中，生殖中心B细胞（GCB）样DLBCL（n = 7）的METTL3表达低于非GCB样DLBCL（n = 30）（P = 0.030）；但在IC-PCNSL患者中，GCB样DLBCL和非GCB样DLBCL的METTL3表达无明显差异（P = 0.670）。虽然感染和未感染艾滋病毒的 PCNSL 患者表现相似，但艾滋病毒相关 PCNSL 在病理特征（包括 METTL3、Bcl-2、p53 和 EBER）方面与 IC-PCNSL 不同。因此，我们认为，HIV 相关 PCNSL 和 IC-PCNSL 的发病机制可能因宿主免疫状态而异。

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引用次数: 0

Prognostic impact of EGFR expression and immunohistochemistry-based “molecular classification” in bladder cancer 表皮生长因子受体表达和基于免疫组化的 "分子分类 "对膀胱癌预后的影响

IF 1.5 4区医学 Q3 PATHOLOGY

Annals of Diagnostic Pathology

Pub Date : 2024-10-10 DOI: 10.1016/j.anndiagpath.2024.152380

Yusuf Onder Ozsagir , Elif Ozsagir , Eyup Dil , Huseyin Eren , Sevdegul Aydin Mungan , Recep Bedir

Recent genomic studies emphasize the necessity of molecular classification to reflect diverse clinical and pathological characteristics of bladder cancer. Immunohistochemically bladder cancer can be classified into molecular subtypes, including basal, luminal, and p53-like subtypes. Epidermal growth factor receptor (EGFR) is frequently expressed in basal-type bladder cancers and is associated with poor prognosis. In our study, 88 urothelial carcinoma cases were retrospectively analyzed, molecularly subtyped using CK5/6, GATA3, p16 immunohistochemistry and examined for EGFR expressions as well as clinical and histopathological features. Tumor cell scores ≥20 % considered positive, classifying cases as luminal (GATA3-positive), basal (CK5/6-positive), double-positive (both-positive), or double-negative (both-negative). Further division of luminal and basal cases was based on p16 status: luminal-p53 or basal-p53 (p16-positive) and luminal-non-p53 or basal-non-p53 (p16-negative). Among the cases, 4 (4 %) were double-negative, 48 (55 %) luminal-non-p53, 21 (24 %) luminal-p53, 5 (6 %) basal-non-p53, 3 (3 %) basal-p53, and 7 (8 %) double-positive. Our findings revealed that basal-non-p53 type bladder cancer is associated with poor prognosis, muscle invasion, and high-grade cytology. Basal-p53 and double-negative types exhibited less aggressive features compared to basal-non-p53 types, with associations observed with lamina propria invasion and high-grade cytology. Luminal-p53 type demonstrated higher recurrence rates. Luminal-non-p53 type displayed the least aggressive characteristics, often associated with papillary histopathology. EGFR expression was found to be high in basal-non-p53 type and was further correlated with adverse prognostic indicators, lamina propria invasion, and high-grade cytology. The identification of molecular subtypes and EGFR expression through immunohistochemistry, alongside traditional bladder cancer classifications, enhances tumor behavior prediction and supports effective clinical management.

最近的基因组研究强调，有必要进行分子分类，以反映膀胱癌不同的临床和病理特征。免疫组化法可将膀胱癌分为分子亚型，包括基底型、管腔型和 p53 样亚型。表皮生长因子受体（EGFR）常在基底型膀胱癌中表达，与预后不良有关。我们的研究对 88 例尿路上皮癌病例进行了回顾性分析，利用 CK5/6、GATA3、p16 免疫组织化学法进行了分子亚型划分，并检查了表皮生长因子受体的表达以及临床和组织病理学特征。肿瘤细胞评分≥20%为阳性，将病例分为管腔型（GATA3阳性）、基底型（CK5/6阳性）、双阳性（均阳性）或双阴性（均阴性）。根据 p16 状态进一步划分管腔和基底病例：管腔-p53 或基底-p53（p16 阳性）和管腔-非 p53 或基底-非 p53（p16 阴性）。其中，4 例（4%）为双阴性，48 例（55%）为管腔-非 p53，21 例（24%）为管腔-p53，5 例（6%）为基底-非 p53，3 例（3%）为基底-p53，7 例（8%）为双阳性。我们的研究结果表明，基底-非 p53 型膀胱癌与预后不良、肌肉侵犯和高级别细胞学相关。与基底-非 53 型膀胱癌相比，基底-53 型和双阴性型膀胱癌的侵袭性较低，与固有层浸润和高级别细胞学相关。基底-p53 型的复发率较高。基底-非p53型的侵袭性最小，通常与乳头状组织病理学有关。研究发现，表皮生长因子受体（EGFR）的表达在基底-非p53型中较高，并与不良预后指标、固有层侵犯和高级别细胞学进一步相关。通过免疫组化鉴定分子亚型和表皮生长因子受体表达，再加上传统的膀胱癌分类，可提高肿瘤行为预测能力，支持有效的临床治疗。

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引用次数: 0

The utility of the mHAI scoring system in pediatric autoimmune hepatitis diagnosis and its association with treatment response mHAI 评分系统在小儿自身免疫性肝炎诊断中的实用性及其与治疗反应的关系

IF 1.5 4区医学 Q3 PATHOLOGY

Annals of Diagnostic Pathology

Pub Date : 2024-10-10 DOI: 10.1016/j.anndiagpath.2024.152381

Wei Chen , Gillian Noel , Mansi Amin , Fengming Chen

Autoimmune hepatitis (AIH) is a chronic inflammatory autoimmune disease with either acute or chronic presentation. Previous scoring systems have primarily focused on chronic hepatitis, but none have been validated in an acute setting of pediatric patients. This study aimed to: 1) summarize the clinicopathologic characteristics of pediatric AIH patients; 2) assess if the modified Hepatic Activity Index (mHAI) can be used in both acute and chronic presentations of pediatric AIH; 3) evaluate the association of initial mHAI scores with treatment response at various endpoints. Thirty-one pediatric AIH patients were categorized into acute and chronic presentation groups. Biopsies were reviewed using the mHAI grading and staging system. AIH treatment endpoints were analyzed: 4 weeks (response vs. non-response), 6 months (complete vs. insufficient response), and approximately 12 months (histological remission vs. non-remission). Patients with acute AIH had higher mean mHAI scores and more prominent interface activity. Those achieving complete response at 6 months had significantly higher mean mHAI scores compared to those with an insufficient response. Notably, patients demonstrating fibrosis reversal at the 1-year follow-up often had higher initial mHAI scores. The mHAI can be used to evaluate acute and chronic presentations of pediatric AIH. Acute pediatric AIH has a higher mHAI score with more severe activity. The patients with a higher mHAI have a greater likelihood of achieving a complete response to treatment at 6 months and subsequent improvement in fibrosis status.

自身免疫性肝炎（AIH）是一种慢性炎症性自身免疫疾病，可表现为急性或慢性。以往的评分系统主要针对慢性肝炎，但没有一个系统在急性期儿科患者中得到验证。本研究旨在1）总结儿科 AIH 患者的临床病理特征；2）评估改良肝活动指数（mHAI）是否可用于急性和慢性表现的儿科 AIH；3）评估初始 mHAI 评分与不同终点的治疗反应之间的关联。31名小儿AIH患者被分为急性和慢性两组。使用 mHAI 分级和分期系统对活检进行复查。对 AIH 治疗终点进行了分析：4 周（应答与无应答）、6 个月（完全应答与应答不足）和大约 12 个月（组织学缓解与非缓解）。急性AIH患者的平均mHAI评分更高，界面活动更突出。与反应不充分的患者相比，在6个月时获得完全反应的患者的平均mHAI评分明显更高。值得注意的是，在1年随访中显示纤维化逆转的患者，其最初的mHAI评分往往更高。mHAI 可用于评估小儿 AIH 的急性和慢性表现。急性小儿 AIH 的 mHAI 分值越高，病情活动越严重。mHAI 较高的患者更有可能在 6 个月时对治疗做出完全反应，随后纤维化状况得到改善。

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引用次数: 0

Clinicopathologic features and tumor immune microenvironment of lymphocyte-rich hepatocellular carcinoma 富含淋巴细胞肝癌的临床病理特征和肿瘤免疫微环境

IF 1.5 4区医学 Q3 PATHOLOGY

Annals of Diagnostic Pathology

Pub Date : 2024-10-10 DOI: 10.1016/j.anndiagpath.2024.152382

Yi-Wang Zhang , Chang Zhao , Bo-Jing Su , Wei-Zheng Lin , Wei-Min Liu , Jing Liang , Chun-Kui Shao , Na Cheng , Jian-Ning Chen

Lymphocyte-rich hepatocellular carcinoma (LR-HCC) is a rare variant of HCC characterized by pronounced lymphoid infiltration, providing an opportunity to explore the tumor immune microenvironment (TIME) and its potential impact on disease progression and therapy. This study aimed to describe the clinicopathological features and TIME components of LR-HCC to inform more effective treatment strategies. In this study, we present five novel cases of LR-HCC alongside a comprehensive retrospective analysis of 136 previously documented cases. Immunohistochemical evaluation was utilized to systematically assess TIME components and immune checkpoint inhibitor (ICI) targets. Our findings demonstrated a significant predominance of CD3+ T cells over CD20+ B cells (1.5:1, P < 0.001) and a higher frequency of CD8+ cytotoxic T cells compared to Foxp3+ regulatory T cells (2.4:1, P < 0.001), indicating an immune landscape potentially favorable for immunotherapeutic interventions. Programmed cell death ligand 1 (PD-L1) expression was detected in three out of five cases using the VENTANA SP263 assay, suggesting potential responsiveness to ICIs. A pooled analysis of 38 cases showed a 5-year overall survival rate of 73.6 %, which is notably lower than previously reported rates (>90 %), with 29.4 % of patients experiencing postoperative recurrence or lymph node metastasis. Multivariate analysis identified tumor size as an independent predictor of overall survival. These findings emphasize the relevance of TIME characteristics in understanding LR-HCC and point to promising avenues for targeted and immune-based therapies, contributing to the optimization of clinical management for this distinct cancer subtype.

富淋巴细胞肝细胞癌（LR-HCC）是一种罕见的HCC变异型，其特点是明显的淋巴细胞浸润，为探索肿瘤免疫微环境（TIME）及其对疾病进展和治疗的潜在影响提供了机会。本研究旨在描述 LR-HCC 的临床病理特征和 TIME 成分，为更有效的治疗策略提供依据。在本研究中，我们在对 136 例既往病例进行全面回顾性分析的同时，还介绍了五例新的 LR-HCC 病例。我们利用免疫组化评估系统地评估了TIME成分和免疫检查点抑制剂（ICI）靶点。我们的研究结果表明，CD3+ T细胞明显多于CD20+ B细胞（1.5:1, P <0.001），CD8+细胞毒性T细胞多于Foxp3+调节性T细胞（2.4:1, P <0.001），这表明免疫格局可能有利于免疫治疗干预。使用 VENTANA SP263 检测法，5 例病例中有 3 例检测到程序性细胞死亡配体 1（PD-L1）表达，这表明患者可能对 ICIs 有反应。对38例病例的汇总分析显示，5年总生存率为73.6%，明显低于之前报道的比率（90%），29.4%的患者术后复发或淋巴结转移。多变量分析发现，肿瘤大小是总生存率的独立预测因素。这些发现强调了TIME特征与了解LR-HCC的相关性，并为靶向和免疫疗法指明了前景广阔的途径，有助于优化这一独特癌症亚型的临床治疗。

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